In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 51, No. 3 ( 2007-03), p. 805-811
Abstract:
Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of β-lactamase-producing K. pneumoniae strains highlight the need to develop new therapeutic strategies. In this study, we developed antisense peptide nucleic acids (PNAs) conjugated to the (KFF) 3 K peptide and investigated whether they could mediate gene-specific antisense effects in K. pneumoniae . No outer membrane permeabilization was observed with antisense PNAs when used alone. Antisense peptide-PNAs targeted at two essential genes, gyrA and ompA , were found to be growth inhibitory at concentrations of 20 μM and 40 μM, respectively. Mismatched antisense peptide-PNAs with sequence variations of the gyrA and ompA genes when used as controls were not growth inhibitory. Bactericidal effects exerted by peptide-anti- gyrA PNA and peptide-anti- ompA PNA on cells were observed within 6 h of treatment. The antisense peptide-PNAs specifically inhibited expression of DNA gyrase subunit A and OmpA from the respective targeted genes in a dose-dependent manner. Both antisense peptide-PNAs cured IMR90 cell cultures that were infected with K. pneumoniae (10 4 CFU) in a dose-dependent manner without any noticeable toxicity to the human cells.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.00709-06
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2007
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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